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Objectives: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed., Design: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science., Setting: Not applicable., Patients: Patients with or at risk for PARDS., Interventions: None., Measurements and Main Results: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%., Conclusions: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients., Competing Interests: Dr. Barbaro is currently receiving grant support (R01 HL153519; R01 HD015434) from the National Institutes of Health (NIH); he is currently Chair of the Extracorporeal Life Support Organization Registry. Dr. Bembea receives research funding to her institution from the NIH/National Institute of Neurological Disorders and Stroke (R01NS106292) and the Grifols Investigator Sponsored Research Grant. She serves as Chair of the Scientific Committee of the Pediatric Acute Lung Injury and Sepsis Investigators Research Network. Dr. Cheifetz is a medical consultant for Phillips and Medtronic. His institution receives research grant funding from the NIH. Dr. Cruces received funding from the Chilean Ministry of Sciences (Fondecyt 1220322). Dr. Curley received funding from the NIH (UH3HL141736, R01HD098269, R01HL149910, R01HL153519, R01HD104618). Dr. Dahmer received funding from the NIH (National Institute of Child Health and Human Development [NICHD], R21 HD097387; National Heart, Lung and Blood Institute [NHLBI] R01 HL149910). Dr. Dalton received funding from the Department of Defense (No. 13363072). She is a consultant for Innovative Extracorporeal Membrane Oxygenation Concepts, Hemocue, Entegrion, Medtronic, and advisory board member for Abiomed. Dr. Emeriaud’s research program is supported by the Fonds de Recherche du Québec-Santé and the Quebec Respiratory Health Network. Dr. Emeriaud is leading a study, which is financially supported by Maquet. Dr. Jouvet’s research program and salary is supported by the Fonds de Recherche du Québec-Santé and the Quebec Respiratory Health Network. Dr. Jouvet is leading studies, which is financially supported by VitalTracer, Dymedso and public financial agencies (Canadian Foundation for innovation, Institut TransMedTech, Quebec Ministry of Health, Sainte-Justine Hospital). Dr. Killien received funding from the NIH (NICHD K23HD100566). Dr. Kneyber received research funding from the NIH/NICHD (UG3 HL141736-01/U24 HL141723-01) and ZorgOnderzoek Nederland and the area Medical (848041002), Stichting Vrienden Beatrix Kinderziekenhuis, Fonds NutsOhra, University Medical Center Groningen, VU University Medical Center, and the Royal Academy of Dutch Sciences (TerMeulen stipend). Dr. Kneyber’s research program is technically supported by Vyaire, Applied Biosignals, and Timpl. Dr. Kneyber received honoraria from Vyaire. Dr. Kneyber serves as consultant for Metran and served as consultant for Vyaire. Dr. Kudchadkar received funding to her institution from the NIH/NICHD (R01HD103811 & R21HD093369) and the Donaghue Foundation. Dr. López-Fernández is funded by an academic grant from the Instituto de Salud Carlos III, Madrid, Spain (PI19/00141). Dr. Maddux received funding to her institution from the NIH/NICHD (K23HD096018). Dr. Morrow has received honoraria for Continuing Medical Education presentations from EduPro Health. Her research is part-funded by the National Research Foundation of South Africa, through the Incentive Funding for Rated Researchers program. Dr. Nadkarni receives unrestricted research grants to his institution from the NIH, U.S. Department of Defense, Agency for Healthcare Research and Quality, Laerdal Foundation, RQI Partners, Zoll Medical, Defibtech, HeartHero, and Nihon-Kohden. Dr. Nadkarni is an elected member of the Executive Committee (Council) of the Society of Critical Care Medicine. Dr. Napolitano research and consulting relationships with: Drager, Timpel, VERO-Biotech, Actuated Medical, and Philips/Respironics. Dr. Pons has been on the speaker’s bureau of Philips, ResMed and Fisher & Paykel; Hospital Sant Joan de Déu has received disposable material from these companies. Dr. Randolph receives funding from the Centers for Disease Control and Prevention, NIH (National Institute of Allergy and Infectious Diseases AI154470). Dr. Rowan receives funding from the NHLBI (NHLBI K23HL150244). Dr. Sanchez-Pinto received funding from the NIH (NICHD R01 HD105939). Dr. Sauthier research program and salary is supported by the Fonds de Recherche du Québec-Santé. Dr. Takeuchi receives funding from Japan Society for the Promotion of Science grant (KAKENHI 21K09063). Dr. Tse receives research funding to her institution from the Canadian Institute of Health Research and salary support from the Fonds de Recherche du Québec—Santé. Dr. Watson receives research funding to his institution from the NIH. Dr. Zimmerman received research funding from NIH and Biomedical Advanced Research and Development Authority; royalties from Elsevier Publishing. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objectives: Previous studies report worse short-term outcomes with hypoglycemia in critically ill children. These studies relied on intermittent blood glucose measurements, which may have introduced detection bias. We analyzed data from the Heart And Lung Failure-Pediatric INsulin Titration trial to determine the association of hypoglycemia with adverse short-term outcomes in critically ill children., Design: Nested case-control study., Setting: Thirty-five PICUs. A computerized algorithm that guided the timing of blood glucose measurements and titration of insulin infusion, continuous glucose monitors, and standardized glucose infusion rates were used to minimize hypoglycemia., Patients: Nondiabetic children with cardiovascular and/or respiratory failure and hyperglycemia. Cases were children with any hypoglycemia (blood glucose < 60 mg/dL), whereas controls were children without hypoglycemia. Each case was matched with up to four unique controls according to age group, study day, and severity of illness., Interventions: None., Measurements and Main Results: A total of 112 (16.0%) of 698 children who received the Heart And Lung Failure-Pediatric INsulin Titration protocol developed hypoglycemia, including 25 (3.6%) who developed severe hypoglycemia (blood glucose < 40 mg/dL). Of these, 110 cases were matched to 427 controls. Hypoglycemia was associated with fewer ICU-free days (median, 15.3 vs 20.2 d; p = 0.04) and fewer hospital-free days (0 vs 7 d; p = 0.01) through day 28. Ventilator-free days through day 28 and mortality at 28 and 90 days did not differ between groups. More children with insulin-induced versus noninsulin-induced hypoglycemia had zero ICU-free days (35.8% vs 20.9%; p = 0.008). Outcomes did not differ between children with severe versus nonsevere hypoglycemia or those with recurrent versus isolated hypoglycemia., Conclusions: When a computerized algorithm, continuous glucose monitors and standardized glucose infusion rates were used to manage hyperglycemia in critically ill children with cardiovascular and/or respiratory failure, severe hypoglycemia (blood glucose < 40 mg/dL) was uncommon, but any hypoglycemia (blood glucose < 60 mg/dL) remained common and was associated with worse short-term outcomes.

Objectives: The 2009-2010 influenza A (H1N1pdm09) pandemic caused substantial morbidity and mortality among young patients; however, mortality estimates have been confounded by regional differences in eligibility criteria and inclusion of selected populations. In 2013-2014, H1N1pdm09 became North America's dominant seasonal influenza strain. Our objective was to compare the baseline characteristics, resources, and treatments with outcomes among critically ill patients with influenza A (H1N1pdm09) in Mexican and Canadian hospitals in 2014 using consistent eligibility criteria., Design: Observational study and a survey of available healthcare setting resources., Setting: Twenty-one hospitals, 13 in Mexico and eight in Canada., Patients: Critically ill patients with confirmed H1N1pdm09 during 2013-2014 influenza season., Interventions: None., Measurements and Main Results: The main outcome measures were 90-day mortality and independent predictors of mortality. Among 165 adult patients with H1N1pdm09-related critical illness between September 2013 and March 2014, mean age was 48.3 years, 64% were males, and nearly all influenza was community acquired. Patients were severely hypoxic (median PaO2-to-FIO2 ratio, 83 mm Hg), 97% received mechanical ventilation, with mean positive end-expiratory pressure of 14 cm H2O at the onset of critical illness and 26.7% received rescue oxygenation therapy with prone ventilation, extracorporeal life support, high-frequency oscillatory ventilation, or inhaled nitric oxide. At 90 days, mortality was 34.6% (13.9% in Canada vs 50.5% in Mexico, p < 0.0001). Independent predictors of mortality included lower presenting PaO2-to-FIO2 ratio (odds ratio, 0.89 per 10-point increase [95% CI, 0.80-0.99]), age (odds ratio, 1.49 per 10 yr increment [95% CI, 1.10-2.02]), and requiring critical care in Mexico (odds ratio, 7.76 [95% CI, 2.02-27.35]). ICUs in Canada generally had more beds, ventilators, healthcare personnel, and rescue oxygenation therapies., Conclusions: Influenza A (H1N1pdm09)-related critical illness still predominantly affects relatively young to middle-aged patients and is associated with severe hypoxemic respiratory failure. The local critical care system and available resources may be influential determinants of patient outcome.

Objective: To investigate the possibility of pediatric intensive care unit shortfalls, using pandemic models for a range of attack rates and durations. The emergence of the swine origin pH1N1 virus has led to concerns about shortfalls in our ability to provide pediatric ventilation and critical care support., Design: Modeling of pediatric intensive care demand based on pH1N1 predictions using simulation techniques., Setting: Simulation laboratory., Patients: None., Interventions: None., Measurements and Main Results: Data collected during the first wave of the pH1N1 in children in Canada were applied to several second wave pandemic models to explore potential pediatric intensive care unit ventilatory demands for Canada and to investigate the impact of vaccination upon these demands. In almost all cases studied, even for relatively low attack rates of 15%, significant pediatric intensive care unit shortages would be expected to occur. Vaccination strategies targeting 50% of the population significantly reduced demand, but shortages may still be expected. Although shortfalls can occur in all provinces, Ontario and British Columbia may experience the greatest supply-demand difference, even at low attack rates., Conclusion: Reducing the attack rate among children, whether through vaccination or additional measures, such as social distancing, will be critical to ensure sufficient pediatric intensive care unit capacity for continued pediatric care.

Objectives: To describe mechanical ventilation strategies in acute lung injury and to estimate the number of eligible patients for clinical trials on mechanical ventilation management. In contrast to adult medicine, there are few clinical trials to guide mechanical ventilation management in children with acute lung injury., Design: A cross-sectional study for six 24-hr periods from June to November 2007., Setting: Fifty-nine pediatric intensive care units in 12 countries in North America and Europe., Patients: We identified children meeting acute lung injury criteria and collected detailed information on illness severity, mechanical ventilatory support, and use of adjunctive therapies., Interventions: None., Measurements and Main Results: Of 3823 patients screened, 414 (10.8%) were diagnosed with acute lung injury by their treating physician, but only 165 (4.3%) patients met prestablished inclusion/exclusion criteria to this trial and, therefore, would have been eligible for a clinical trial. Of these, 124 (75.2%) received conventional mechanical ventilation, 27 (16.4%) received high-frequency oscillatory ventilation, and 14 (8.5%) received noninvasive mechanical ventilation. In the conventional mechanical ventilation group, 43.5% were ventilated in a pressure control mode with a mean tidal volume of 8.3 ± 3.3 mL/kg; and there was no clear relationship between positive end-expiratory pressure and Fio2 delivery in the conventional mechanical ventilation group. Use of adjunctive treatments, including nitric oxide, prone positioning, surfactant, hemofiltration, recruitment maneuvers, steroids, bronchodilators, and fluid restriction, was highly variable., Conclusions: Our study reveals inconsistent mechanical ventilation practice and use of adjunctive therapies in children with acute lung injury. Pediatric clinical trials assessing mechanical ventilation management are needed to generate evidence to optimize outcomes. We estimate that a large number of centers (∼60) are needed to conduct such trials; it is imperative, therefore, to bring about international collaboration.

Objective: To describe characteristics, treatment, and outcomes of critically ill children with influenza A/pandemic influenza A virus (pH1N1) infection in Canada., Design: An observational study of critically ill children with influenza A/pH1N1 infection in pediatric intensive care units (PICUs)., Setting: Nine Canadian PICUs., Patients: A total of 57 patients admitted to PICUs between April 16, 2009 and August 15, 2009., Interventions: None., Measurements and Main Results: Characteristics of critically ill children with influenza A/pH1N1 infection were recorded. Confirmed intensive care unit cases were compared with a national surveillance database containing all hospitalized pediatric patients with influenza A/pH1N1 infection. Risk factors were assessed with a Cox proportional hazard model. The PICU cohort and national surveillance data were compared, using chi-square tests. Fifty-seven children were admitted to the PICU for community-acquired influenza A/pH1N1 infection. One or more chronic comorbid illnesses were observed in 70.2% of patients, and 24.6% of patients were aboriginal. Mechanical ventilation was used in 68% of children, 20 children (35.1%) had acute lung injury on the first day of admission, and the median duration of ventilation was 6 days (range, 0-67 days). The PICU mortality rate was 7% (4 of 57 patients). When compared with nonintensive care unit hospitalized children, PICU children were more likely to have a chronic medical condition (relative risk, 1.73); aboriginal ethnicity was not a risk factor of intensive care unit admission., Conclusions: During the first outbreak of influenza A/pH1N1 infection, when the population was naïve to this novel virus, severe illness was common among children with underlying chronic conditions and aboriginal children. Influenza A/pH1N1-related critical illness in children was associated with severe hypoxemic respiratory failure and prolonged mechanical ventilation. However, this higher rate and severity of respiratory illness did not result in an increased mortality when compared with seasonal influenza.

As a critical care community, we have an obligation to provide not only clinical care but also the research that guides initial and subsequent clinical responses during a pandemic. There are many challenges to conducting such research. The first is speed of response. However, given the near inevitability of certain events, for example, viral respiratory illness such as the 2009 pandemic, geographically circumscribed natural disasters, or acts of terror, many study and trial designs should be preplanned and modified quickly when specific events occur. Template case report forms should be available for modification and web entry; centralized research ethics boards and funders should have the opportunity to preview and advise on such research beforehand; and national and international research groups should be prepared to work together on common studies and trials for common challenges. We describe the early international critical care research response to the influenza A 2009 (H1N1) pandemic, including specifics of observational study case report form, registry, and clinical trial design, cooperation of international critical care research organizations, and the early results of these collaborations.

Objective: To evaluate the applicability, tolerance, and efficacy of a closed-loop protocol to wean children from mechanical ventilation., Design: Prospective single-center pilot study., Setting: Tertiary care university hospital., Patients: Twenty mechanically ventilated children aged between 1 and 17 yrs, with a body weight > or =10 kg, no inotropes, and no heavy sedation., Interventions: Patients were weaned in pressure support mode by a closed-loop computerized protocol (closed-loop protocol) that interprets clinical data in real time and controls pressure support levels., Measurements and Main Results: The closed-loop protocol applicability and tolerance were evaluated. The efficacy of this protocol was evaluated by comparing the duration of mechanical ventilation with a historical group of 20 patients weaned with a clinician-decision protocol. The closed-loop protocol successfully decreased pressure support ventilation in 16 children, recommended separation from the ventilator in 14 children, and did not cause any serious adverse events. Mechanical ventilation duration was 5.1 +/- 4.2 days in the closed-loop group and 6.7 +/- 11.5 days (mean +/- sd) in the clinician-decision group (p = .33) with no difference in the need for reintubation or noninvasive mechanical ventilation (one of 20 and four of 20, respectively; p = .20)., Conclusions: A closed-loop protocol was successfully used to wean children from mechanical ventilation. Further studies are required to assess the impact of this novel therapeutic strategy on the length of mechanical ventilation.